2026-04-14T03:36:03Zhttps://recercat.cat/oai/request

oai:recercat.cat:10230/532622025-12-12T01:49:05Zcom_2072_6col_2072_452952

00925njm 22002777a 4500 dc Blackwell, Danielle L. author Fraser, Sherri D. author Caluseriu, Oana author Vivori, Claudia, 1989- author Tyndall, Amanda V. author Lamont, Ryan E. author Parboosingh, Jillian S. author Innes, A. Micheil author Bernier, François P. author Childs, Sarah J. author 2022-05-25T10:16:20Z 2022-05-25T10:16:20Z 2022 Mutations in RNA-binding proteins can lead to pleiotropic phenotypes including craniofacial, skeletal, limb, and neurological symptoms. Heterogeneous nuclear ribonucleoproteins (hnRNPs) are involved in nucleic acid binding, transcription, and splicing through direct binding to DNA and RNA, or through interaction with other proteins in the spliceosome. We show a developmental role for Hnrnpul1 in zebrafish, resulting in reduced body and fin growth and missing bones. Defects in craniofacial tendon growth and adult-onset caudal scoliosis are also seen. We demonstrate a role for Hnrnpul1 in alternative splicing and transcriptional regulation using RNA-sequencing, particularly of genes involved in translation, ubiquitination, and DNA damage. Given its cross-species conservation and role in splicing, it would not be surprising if it had a role in human development. Whole-exome sequencing detected a homozygous frameshift variant in HNRNPUL1 in 2 siblings with congenital limb malformations, which is a candidate gene for their limb malformations. Zebrafish Hnrnpul1 mutants suggest an important developmental role of hnRNPUL1 and provide motivation for exploring the potential conservation of ancient regulatory circuits involving hnRNPUL1 in human development. We thank the Alberta Children’s Hospital Research Institute for funding for DB and SF through the MORPH project. Operating funding was received from the Canadian Institute of Health Research Institute of Genetics Rare Disease Models and Mechanisms (180309-001-001) and from the National Science and Engineering Research Council (RGPIN/07176-2019) to SJC Genètica Empalmament (Genètica) Escoliosi Hnrnpul1 controls transcription, splicing, and modulates skeletal and limb development in vivo